Einfluss verschiedener KRAS-Mutationen auf das Ansprechen von kolorektalen Zellen auf eine  5-Fluorouracil-basierende Radiochemotherapie in Anwesenheit von Rezeptortyrosinkinase-Inhibitoren

Wiedmann, Simon

dc.contributor.advisor	Burfeind, Peter Prof. Dr.
dc.contributor.author	Wiedmann, Simon
dc.date.accessioned	2022-02-14T14:28:29Z
dc.date.available	2022-02-21T00:50:03Z
dc.date.issued	2022-02-14
dc.identifier.uri	http://resolver.sub.uni-goettingen.de/purl?ediss-11858/13866
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-43
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc	610	de
dc.title	Einfluss verschiedener KRAS-Mutationen auf das Ansprechen von kolorektalen Zellen auf eine 5-Fluorouracil-basierende Radiochemotherapie in Anwesenheit von Rezeptortyrosinkinase-Inhibitoren	de
dc.type	doctoralThesis	de
dc.title.translated	Mutations in KRAS influence the behavior and response of colorectal cancer cells to 5-FU based radiochemotherapy combined with receptor tyrosine kinase inhibitors	de
dc.contributor.referee	Burfeind, Peter Prof. Dr.
dc.date.examination	2022-02-15	de
dc.description.abstracteng	Aims: Mutations of the proto-oncogene KRAS are supposed to lead to an increased activity of KRAS inducing a constitutive activation of the downstream MAPK signaling pathway. The aim of the work was to investigate the behavior of colorectal cancer cell line SW48 with different mutations in KRAS and their response to a combined radiochemotherapy (RCT) in the presence of different receptor tyrosin kinase inhibitors (RTKI). Methods: The colorectal cancer cell line SW48 carrying either KRAS wild-type or the KRAS mutations p. G12V, p. G12D and p. G13D were used. Cell proliferation, migration and invasion assays were performed to further characterize the cells. Activation of MAPK signaling pathway was assessed by Western blots. The sensitivity of the cell lines to a 5-FU based RCT and in the presence of RTKIs Erlotinib und AEW541 was demonstrated by colony formation assays. Results: No difference in proliferation was seen between cells with KRAS wild-type and KRAS mutations. Cells with p. G12V demonstrated the most aggressive behavior in migration and invasion assays. No relevant difference in the phosphorylation status of MAPK component ERK was observed after different stimuli. The most sensitivity to a 5-FU based RCT in the presence of RTKI was found in SW48 cells carrying the p. G13D mutation. SW48 cells carrying the p. G12D showed the most resistance to a 5-FU based RCT in the presence of RTKI. Conclusion: In our experiments a constitutive activation of the MAPK pathway could not be shown despite the different KRAS mutated SW48 cells. SW48 cells with p. G12V demonstrated the most aggressive behavior. Further, we observed that different KRAS mutations have different sensitivity to a 5-FU based RCT in combination with RTKI.	de
dc.contributor.coReferee	Gaedcke, Jochen Prof. Dr.
dc.subject.eng	colorectal cancer	de
dc.subject.eng	KRAS mutation	de
dc.subject.eng	SW48 cells	de
dc.subject.eng	radiochemotherapy	de
dc.subject.eng	receptor tyrosine kinase inhibitors	de
dc.identifier.urn	urn:nbn:de:gbv:7-ediss-13866-1
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	:Humangenetik / Teratologie - Allgemein- und Gesamtdarstellungen (PPN619875259)	de
dc.description.embargoed	2022-02-21	de
dc.identifier.ppn	1794694684

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